How exactly do mutations cause genetic variation in bilaterians?

Question

I am trying to understand how mutations cause genetic variance, and I'm stuck on one issue that I'm going to try my best to explain. (I am specifically talking about mutations that cause a phenotypical change). The question is focused on organisms with a distinct germ-line.

My issue is with trying to understand where mutations need to occur to cause variation. For example, does the mutation need to occur in the DNA of either the specific sperm or the specific egg that gave rise to you?

The body of an organism obviously has a vast, vast number of cells. If a mutation occurred in just one of these cells, then surely it wouldn't have any phenotypical effect. Even as an infant or an embryo, if a mutation occurs in just one of your many cells, that is unlikely to cause any phenotypical changes (phenotypical variance) as your body develops. So, is the only way for a mutation to have a phenotypical effect is for it to occur in the gametes that produced you? That way, all of your DNA would inherit the mutation, since all of your DNA would be replicated from the DNA of the sperm and egg.

Answer 1

For example, does the mutation need to occur in the DNA of either the specific sperm or the specific egg that gave rise to you?

To give rise to heritable genetic variation in the sense that it's a mutation that exists in all of your cells and is transmitted (with some probability) to your offspring, yes, it must come from the gametes, with the caveat that it need not occur specifically in the gamete, but in any of the cells giving rise to that gamete in either parent. I suppose it could also occur in the fertilized egg cell, and mutations shortly thereafter may produce a chimera where a substantial fraction, but not all cells carry that mutation, but as mutations are most common during cell division I think it's okay to simplify a bit and presume the source is the gametes for most heritable mutations.

Estimates of how many of these mutations exist per human fertilized egg (relative to their parent genomes) vary, but you can assume that each human has something on the order of dozens in coding regions that their parents lack, plus others in other areas of the genome. A whole human organism has far, far more mutations, and these cause issues with aging and cancer in their cells, but these are not typically heritable.

The number of mutations per replication depends on genome size and also the stringency of that organism's replication machinery. In general, complex eukaryotes have stronger systems for correcting replication errors, so you can expect bacteria to have higher rates of mutation. Some related reading:

Correlation between genome size and mutation rate?

How much variation in mutation rate in there in the human genome?

Bacterial division and mutation rate

Mutation rate in viruses

Veltman, J. A., & Brunner, H. G. (2012). De novo mutations in human genetic disease. Nature Reviews Genetics, 13(8), 565-575.

Each generation (per individual), approximately 74 de novo single-nucleotide variants (SNVs), three novel indels (small insertions or deletions) and 0.02 larger copy number variants (CNVs) arise in our genome

Ségurel, L., Wyman, M. J., & Przeworski, M. (2014). Determinants of mutation rate variation in the human germline. Annu Rev Genomics Hum Genet, 15(1), 47-70.